BACKGROUND: Alternative splicing of the interleukin-5 receptor alpha (IL-5Ralpha)-subunit leads to the generation of a signalling, membrane-anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL-5 in eosinophil function, we investigated SOL IL-5Ralpha expression pattern in an eosinophil-associated disease such as nasal polyposis (NP). METHODS: An SOL IL-5Ralpha enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma. RESULTS: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL-5Ralpha protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up-regulation of SOL IL-5Ralpha in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real-time reverse-transcriptase PCR procedure. CONCLUSIONS: This report demonstrates SOL IL-5Ralpha transcript and protein up-regulation in NP. Soluble IL-5Ralpha differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Ralpha is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.
BACKGROUND: Alternative splicing of the interleukin-5 receptor alpha (IL-5Ralpha)-subunit leads to the generation of a signalling, membrane-anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL-5 in eosinophil function, we investigated SOL IL-5Ralpha expression pattern in an eosinophil-associated disease such as nasal polyposis (NP). METHODS: An SOL IL-5Ralpha enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma. RESULTS: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL-5Ralpha protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up-regulation of SOL IL-5Ralpha in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real-time reverse-transcriptase PCR procedure. CONCLUSIONS: This report demonstrates SOL IL-5Ralpha transcript and protein up-regulation in NP. Soluble IL-5Ralpha differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Ralpha is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.
Authors: Todd M Wilson; Irina Maric; Juhi Shukla; Margaret Brown; Carlo Santos; Olga Simakova; Paneez Khoury; Michael P Fay; Alexander Kozhich; Roland Kolbeck; Dean D Metcalfe; Amy D Klion Journal: J Allergy Clin Immunol Date: 2011-07-16 Impact factor: 10.793
Authors: Eli O Meltzer; Daniel L Hamilos; James A Hadley; Donald C Lanza; Bradley F Marple; Richard A Nicklas; Claus Bachert; James Baraniuk; Fuad M Baroody; Michael S Benninger; Itzhak Brook; Badrul A Chowdhury; Howard M Druce; Stephen Durham; Berrylin Ferguson; Jack M Gwaltney; Michael Kaliner; David W Kennedy; Valerie Lund; Robert Naclerio; Ruby Pawankar; Jay F Piccirillo; Patricia Rohane; Ronald Simon; Raymond G Slavin; Alkis Togias; Ellen R Wald; S James Zinreich Journal: Otolaryngol Head Neck Surg Date: 2004-12 Impact factor: 3.497
Authors: Eli O Meltzer; Daniel L Hamilos; James A Hadley; Donald C Lanza; Bradley F Marple; Richard A Nicklas; Claus Bachert; James Baraniuk; Fuad M Baroody; Michael S Benninger; Itzhak Brook; Badrul A Chowdhury; Howard M Druce; Stephen Durham; Berrylin Ferguson; Jack M Gwaltney; Michael Kaliner; David W Kennedy; Valerie Lund; Robert Naclerio; Ruby Pawankar; Jay F Piccirillo; Patricia Rohane; Ronald Simon; Raymond G Slavin; Alkis Togias; Ellen R Wald; S James Zinreich Journal: J Allergy Clin Immunol Date: 2004-12 Impact factor: 10.793
Authors: Kathleen M Buchheit; Daniel F Dwyer; Jose Ordovas-Montanes; Howard R Katz; Erin Lewis; Marko Vukovic; Juying Lai; Lora G Bankova; Neil Bhattacharyya; Alex K Shalek; Nora A Barrett; Joshua A Boyce; Tanya M Laidlaw Journal: J Allergy Clin Immunol Date: 2020-03-19 Impact factor: 10.793